A genetic history of the pre-contact Caribbean.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1-3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.

The deposition of islet amyloid polypeptide (hIAPP) fibrils is a hallmark of ß-cell death in type II diabetes. In this study, we employ state-of-the-art MAS solid-state spectroscopy to investigate the previously elusive N-terminal region of hIAPP fibrils, uncovering both rigidity and heterogeneity. Comparative analysis between wild-type hIAPP and a disulfide-deficient variant (hIAPPC2S,C7S) unveils shared fibril core structures yet strikingly distinct dynamics in the N-terminus. Specifically, the variant fibrils exhibit extended ß-strand conformations, facilitating surface nucleation. Moreover, our findings illuminate the pivotal roles of specific residues in modulating secondary nucleation rates. These results deepen our understanding of hIAPP fibril assembly and provide critical insights into the molecular mechanisms underpinning type II diabetes, holding promise for future therapeutic strategies.

Habitat complexity influences neuron number in six species of Puerto Rican Anolis.

Elucidating the selective forces shaping the diversity of vertebrate brains continues to be a major area of inquiry, particularly as it relates to cognition. Historically brain evolution was interpreted through the lens of relative brain size; however, recent evidence has challenged this approach. Investigating neuroanatomy at a finer scale, such as neuron number, can provide new insights into the forces shaping brain evolution in the context of information processing capacity. Ecological factors, such as the complexity of a species' habitat, place demands on cognition that could shape neuroanatomy. In this study, we investigate the relationship between neuron number and habitat complexity in three brain regions across six closely related anole species from Puerto Rico. After controlling for brain mass, we found that the number of neurons increased with habitat complexity across species in the telencephalon and 'rest of the brain,' but not in the cerebellum. Our results demonstrate that habitat complexity has shaped neuroanatomy in the Puerto Rican anole radiation and provide further evidence of the role of habitat complexity in vertebrate brain evolution.

Can my surgeon scope? Trends in endoscopy training volume and experience among general surgery residents in the United States: a nationwide analysis.

INTRODUCTION: Endoscopy is a major part of surgical training. Accreditation Council for Graduate Medical Education (ACGME) has set standards regarding the minimum volume of endoscopy cases required for graduation. However, there is paucity of high-quality data on the number of cases that most surgical graduates perform. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from ACGME-accredited programs from 2010 to 2023. Data on mean number of endoscopy cases, including mean in each subcategory, were retrieved. Mann-Kendall trend test was used to investigate trends in endoscopy experience. RESULTS: Between 2010 and 2023, the mean overall endoscopy procedures per resident remained stable, with 129.5 in 2010 and 132.1 in 2023 (t = 0.429; p-value = 0.037). The majority of these cases were performed as surgeon junior (76.6% in 2010; 80.9% in 2023), while the remaining cases were logged as surgeon chief. The most substantial contribution to the overall volume was from flexible colonoscopy (mean: 64.1 in 2010 and 67.2 in 2023). The volume for colonoscopy remained fairly stable (t = 0.429; p-value = 0.036). This was followed by esophagogastroduodenoscopy (mean: 35.3 in 2010 and 35.5 in 2023), which saw a significant increase in volume (t = 0.890; p-value ≤ 0.001). There was a significant increase in the number of overall upper endoscopic procedures (t = 0.791; p-value ≤ 0.001), while lower endoscopic procedures did not change significantly (t = 0.319; p-value = 0.125). The procedural volume for endoscopic retrograde cholangiography, sigmoidoscopy, cystoscopy/ureteroscopy, laryngoscopy, and bronchoscopy decreased significantly (p-value < 0.05 for all). CONCLUSION: The overall endoscopy volume for general surgery residents has largely remained stable, with a minor increase in esophagogastroduodenoscopy and no change in colonoscopy. Future research should investigate whether simulation-based exercises can bridge the gap between procedural volume and learning curve requirements for endoscopy.

Optimizing decision-making process of benign uretero-enteric anastomotic stricture treatment after radical cystectomy.

PURPOSE: To identify preoperative predictors of endo-urological treatment (EUT) failure while promoting a new diagnostic and therapeutic pathway for benign uretero-enteric anastomosis stricture (UES) management after radical cystectomy (RC). MATERIALS AND METHODS: We relied on a prospectively maintained database including 96 individuals (122 renal units) who developed a benign UES at our institution between 1990 and 2018. UES was classified into two different types according to morphology: FP1 (i.e., sharp or duckbill) and FP2 (i.e., flat or concave). EUT feasibility, success rate, as well as intra and postoperative complications were recorded. Uni- and multivariable logistic regression analysis (MVA) assessed for predictors of EUT failure. RESULTS: Overall, 78 (63.9%) and 32 (26.3%) cases were defined as FP1 and FP2, respectively. EUT was not feasible in 33 (27.1%) cases. After a median follow-up of 50 (IQR 5-240) months, successful treatment was reached only in 15/122 (12.3%) cases. EUT success rates raised when considering short (< 1 cm) (16.8%), FP1 morphology (16.7%) strictures, or the combination of these characteristics (22.4%). Overall, 5 (5.2%) cases had CD ≥ III complications. FP2 (OR: 1.91, 95%CI 1.21-5.31, p = 0.03) and stricture length ≥ 1 cm (OR: 9.08, 95%CI 2.09-65.71, p = 0.009) were associated with treatment failure at MVA. CONCLUSIONS: Endoscopic treatment for benign UES after RC is feasible but harbors a low success rate. Stricture length and radiological morphology of the stricture are related to endoscopic treatment failure. Surgeons should be aware of the stricture features during the preoperative decision-making process to choose the optimal candidate for endoscopic treatment.

Cognitive stimulation of executive functions through computational thinking.

The healthy development of cognitive functions, including executive functions, has been shown to depend mainly on the experiences and learning opportunities of people, especially during childhood. Over the past few years, researchers have been studying the impacts of diverse types of interventions on children's cognitive development in which computational thinking programs are a recent field. This pilot study evaluated the effect of computational thinking training based on the "Programming for Children" program on the executive functions of children aged 10 and 11 years: working memory, inhibition, and planning (N = 30). The results showed that children in the experimental group improved on tests of visuospatial working memory, cognitive inhibition, and sequential planning compared with the control group. However, tests of verbal working memory, memory strategy, and visual spatial planning did not show any observed changes. Although this was an exploratory study, and its findings should be interpreted cautiously due to the small sample size, the findings support the relevance and feasibility of conducting similar larger studies with larger samples.

A Brief Media Intervention Influences Collegiate Males' Attitude and Knowledge Towards Breastfeeding.

Breastfeeding is the optimal source of infant nutrition, yet the mother's decision to breastfeed is complex and influenced by factors including social support and breastfeeding knowledge and attitudes. This study employed a two-group pretest-posttest design to examine whether brief, online video presentations (<2.5 minutes in length) could improve breastfeeding knowledge and attitude among males and compare the outcomes between a knowledge-based and attitude-based intervention. Collegiate male participants (N = 213, 18-40 years of age) demonstrated high breastfeeding exposure (90.1% had friends/family breastfeed) and positive attitudes (89.2% accepted women could breastfeed and work outside home) yet knowledge deficits concerning breastfeeding health benefits were identified. Breastfeeding exposure was positively associated with baseline attitude (r(212)=.186, p = .006 and knowledge (r(212)=.229, p = .001. Both intervention groups reported similar gains in attitude scores; only the knowledge-based intervention reported significant gains in knowledge (M = 1.5, SD = 2.63 vs M = -.07, SD = 1.44, (t = -5.496, df = 211, p < .05). Brief online video presentations may constitute an additional exposure to or nudging toward breastfeeding, and breastfeeding knowledge and attitudes can be positively influenced in young adult males with similar interventions that are affordable and require a minimal time commitment.

Induced Abortion and the Risk of Rh Sensitization.

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Can Sensory Drive Explain the Evolution of Visual Signal Diversity in Terrestrial Species? A Test with Anolis Lizards.

AbstractAnimal signal colors evolve to efficiently stimulate conspecific visual systems. The sensory drive hypothesis proposes that species differences in habitat light conditions favor the evolution of color diversity. The strongest support comes from aquatic systems, while terrestrial systems offer fewer convincing examples. Anolis lizards occupy diverse habitats and signal with a colorful dewlap. Dewlap visibility depends on perceived chromatic contrast with the background. Visual system modeling has shown that red dewlaps are most visible in most habitat types. However, a majority of species possess white or yellow dewlaps. In a recent behavioral study, we showed that low light conditions can sometimes make yellow and white colors more visible by altering chromatic contrast perception with the background. Using 17 Caribbean Anolis species, we showed that cut-on wavelength, a measure of dewlap color in a white to red continuum, correlates with habitat light intensity. Pairwise comparisons revealed that red dewlaps are most visible in bright habitats, whereas yellow and white are more visible in darker habitats. We conclude that sensory drive has contributed to the evolution of dewlap color differences through the interactive effects of total habitat light intensity and chromatic contrast perception and may provide a mechanism for speciation among anoles.

Mask side-effects in long-term CPAP-patients impact adherence and sleepiness: the InterfaceVent real-life study.

BACKGROUND: For some patients, Continuous Positive Airway Pressure (CPAP) remains an uncomfortable therapy despite the constant development of technological innovations. To date, no real life study has investigated the relationship between mask related side-effects (MRSEs) and CPAP-non-adherence (defined as < 4 h/day) or residual-excessive-sleepiness (RES, Epworth-Sleepiness-Scale (ESS) score ≥ 11) in the long-term. METHODS: The InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks). MRSEs were evaluated using visual-analogue-scales, CPAP-data using CPAP-software, sleepiness using ESS. RESULTS: 1484 patients were included in the analysis (72.2% male, median age 67 years (IQ25-75: 60-74), initial Apnea-Hypopnea-Index (AHI) of 39 (31-56)/h, residual AHIflow was 1.9 (0.9-4) events/h), CPAP-treatment lasted 4.4 (2.0-9.7) years, CPAP-usage was 6.8 (5.5-7.8) h/day, the prevalence of CPAP-non-adherence was 8.6%, and the prevalence of RES was 16.17%. Leak-related side-effects were the most prevalent side-effects (patient-reported leaks concerned 75.4% of responders and had no correlation with CPAP-reported-leaks). Multivariable logistic regression analyses evaluating explanatory-variable (demographic data, device/mask data and MRSEs) effects on variables-of-interest (CPAP-non-adherence and RES), indicated for patient-MRSEs significant associations between: (i) CPAP-non-adherence and dry-mouth (p = 0.004); (ii) RES and patient-reported leaks (p = 0.007), noisy mask (p < 0.001), dry nose (p < 0.001) and harness pain (p = 0.043). CONCLUSION: In long-term CPAP-treated patients, leak-related side-effects remain the most prevalent side-effects, but patient-reported leaks cannot be predicted by CPAP-reported-leaks. Patient-MRSEs can be independently associated with CPAP-non-adherence and RES, thus implying a complementary role for MRSE questionnaires alongside CPAP-device-reported-data for patient monitoring. Trial registration InterfaceVent is registered with ClinicalTrials.gov (NCT03013283).

Is the 2013 American Thoracic Society CPAP-tracking system algorithm useful for managing non-adherence in long-term CPAP-treated patients?

BACKGROUND: Whereas telemedicine usage is growing, the only clinical algorithm for Continuous Positive Airway Pressure (CPAP) adherence management is that stipulated by the 2013 American Thoracic Society (ATS). The capacity of the latter to predict non-adherence in long-term CPAP-treated patients has not been validated. METHODS: Patients from the prospective real-life InterfaceVent study (NCT03013283, study conducted in an adult cohort undergoing at least 3 months of CPAP) and eligible for ATS algorithm usage were analysed. The residual device Apnea-Hypopnea-Index (AHIflow) and High Large Leak (HLL) thresholds proposed in the ATS algorithm were evaluated for predicting adherence (i.e. AHIflow > 10/h, HLLs 95th > 24 L/min for ResMed® devices and ResMed® nasal mask, HLLs 95th > 36 l/min for ResMed® devices and ResMed® oronasal masks, HLLs > 1 h for Philips® devices and HHLs > 60 l/min for Fisher & Paykel® devices). Adherence was defined according to the 2013 ATS algorithm (i.e. CPAP use > 4 h/j for at least 70% of days). RESULTS: 650/1484 patients eligible for ATS algorithm usage were analysed (15.38% non-adherent, 74% male with a median (IQ25-75) age of 68 (61-77) years, a body mass index of 30.8 (27.7-34.5) kg/m2, an initial AHI of 39 (31-55) events/h, and CPAP-treatment-duration of 5.1 (2.2-7.8) years). Logistic regression analysis demonstrated no significant relationship between the ATS proposed AHIflow or HLL thresholds and non-adherence. Complementary ROC curve analysis failed to determine satisfactory AHIflow and HLL thresholds. CONCLUSION: When managing non-adherence in long-term CPAP-treated patients, our data do not validate absolute AHIflow or HLL thresholds in general. TRIAL REGISTRATION: The INTERFACE-VENT study is registered on ClinicalTrials.gov (Identifier: study ( NCT03013283 ).

Cell-based assays and molecular dynamics analysis of a boron-containing agonist with different profiles of binding to human and guinea pig beta2 adrenoceptors.

The design of beta2 adrenoceptor (ß2AR) agonists is attractive because of their wide-ranging applications in medicine, and the details of agonist interactions with ß2AR are interesting because it is considered a prototype for G-protein coupled receptors. Preclinical studies for agonist development have involved biological assays with guinea pigs due to a similar physiology to humans. Boron-containing Albuterol derivatives (BCADs) designed as bronchodilators have improved potency and efficacy compared with their boron-free precursor on guinea pig ß2ARs (gpß2ARs), and two of the BCADs (BR-AEA and boronterol) conserve these features on cells expressing human ß2ARs (hß2ARs). The aim of this study was to test the BCAD Politerol on gpß2ARs and hß2ARs in vitro and in silico. Politerol displayed higher potency and efficacy on gpß2AR than on hß2AR in experimental assays, possible explanations are provided based on molecular modeling, and molecular dynamics simulations of about 0.25 µs were performed for the free and bound states adding up to 2 µs in total. There were slight differences, particularly in the role of the boron atom, in the interactions of Politerol with gpß2ARs and hß2ARs, affecting movements of transmembrane domains 5-7, known to be pivotal in receptor activation. These findings could be instrumental in the design of compounds selective for hß2ARs.

Germination in Optimal Conditions as Effective Strategy to Improve Nutritional and Nutraceutical Value of Underutilized Mexican Blue Maize Seeds.

Germination of grains is a bioprocess of emerging interest to improve nutritional and nutraceutical profile of cereals in a natural way. The aim of this work was to identify optimal germination conditions (temperature/duration) for producing a functional blue maize flour with maximum values of protein content (PC), antioxidant activity (AoxA), and total phenolic and anthocyanin contents (TPC, TAC). A central composite rotatable experimental design (response surface methodology) with two factors [Germination temperature (Gtemp, 20-40 °C) / Germination duration (Gdur, 12-220 h)] in five levels was used (13 treatments). Blue maize seeds were soaked in distilled water (25 °C / 12 h) before germination. The sprouts were dried, tempered (25 °C), and ground to obtain germinated blue maize flours (GBMF). The prediction models developed for each response variable showed high coefficients of determination, demonstrating their adequacy to explain the variations in experimental data. Maximum values of PC, AoxA, TPC, and TAC were attained at Gtemp = 26.9 °C / Gdur = 207.7 h. Optimized germinated blue maize flour (OGBMF) presented higher PC (+38.48%), AoxA (ABTS: +192%, ORAC: +160%, DPPH: +148%), TPC (+79%), and TAC (+9.9%) than unprocessed blue maize flour (UBMF). Germination at optimal conditions is an effective strategy to increase the nutritional/nutraceutical quality of blue maize seeds, thus the flour of these germinated seeds could be used for the development of functional foods.

Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the ß2 adrenoceptor.

The development of ß2 adrenoceptor (ß2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50⩽28.02nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.

[Resistant human fasciolasis: report of four patients]. / Fascioliasis hepática humana: resistencia al tratamiento con triclabendazol.

Human fascioliasis is a parasitic zoonosis that affects the liver of human and herbivorous animals. In chronic cases, its diagnosis is confirmed by direct visualization of parasitic eggs in stool examination, by positive testing for Fasciola hepatica antigens in stools, or by direct observation of parasites by endoscopic retrograde cholangiography or surgery. In acute cases, serological reactions as immunoblothing or detection of parasite antigens in the blood are useful. The treatment of choice is triclabendazole. However, parasite resistance in animals, as well as in man, has been reported to this drug. We report four patients in whom the parasitic infection persisted despite a course of treatment with triclabendazole.

Initial Experience in Urological Surgery with a Novel Robotic Technology: Magnetic-Assisted Robotic Surgery in Urology.

Introduction and objective: Magnetic-assisted robotic surgery (MARS) has been developed to maximize patient benefits of minimally invasive surgery while enhancing surgeon control and visualization. MARS platform (Levita Magnetics) comprises two robotic arms that provide control to an external magnetic controller and an off-the-shelf laparoscopic camera. Our aim was to evaluate the safety and efficacy of the MARS platform in laparoscopic renal and adrenal procedure for the first time. Methods: This is a prospective, single-arm, open-label study (Clinical Trials Identifier: NCT05353777) including patients with renal or adrenal pathology analysis, submitted to laparoscopic procedure between April and June 2022. Patients were followed up to 30 days postoperatively. Preoperative, intraoperative, and postoperative data were recorded. Polynomial regression was used to determine the learning curve for docking time. Results: Fifteen cases were performed using the MARS platform (three partial nephrectomies, five total nephrectomies for benign pathology analysis, four radical nephrectomies, and three adrenalectomies) corresponding to 10 women and 5 men (mean age, 55 years [18-77]; average body mass index, 29 cm/m2 [22-39]). No cases required conversion to open procedure and all patients were discharged on the first or second postoperative day. No complications or re-admissions were reported within the first 30 days. All oncologic cases had negative margins. Learning curve was achieved by the fourth case, diminishing docking time from 5.22 (2.6-11.5) to 2.68 minutes (2.1-3.8) (p = 0.002). The learning curve was fitted to a cubic regression (R2 = 0.714). Conclusion: This is the first clinical study demonstrating the safety and versatility of the MARS platform in urologic procedures. The robot was especially useful for tissue retraction, avoiding additional incisions and the need for a surgical assistant while increasing surgeon control and visualization. The learning curve was rapid, achieving a short docking time. MARS is a promising new technology that could be successfully evaluated in other surgeries.

Emotional Regulation Mechanisms of University Students in Group Work Situations.

Universities are active agents of social change through knowledge, providing citizens with the necessary abilities to face professional challenges. This work aims to evaluate and analyse the adaptation of emotional regulation in learning situations of group work in virtual and hybrid (virtual and presential) environments, of a group of students of Physical Activity and Sport Sciences belonging to a Chilean university and a Spanish university. METHOD: A total of 107 students from a Chilean university and a Spanish university, all of them enrolled in the degree in Physical Activity and Sport Sciences, participated in the study. The instrument used was the Adaptative Instrument for Regulation of Emotions questionnaire. RESULTS: The analysis of the data shows that there are some significant differences (p ≤ 0.05), between the groups of students who worked virtually and those who worked in hybrid situations, in the aspects related to personal motivations (learn from my classmates, not to disappoint my working group, and enjoying the experience of working in a group). The students who worked online resolved conflicts mainly through individual regulation mechanisms with significant differences in relation to the students who worked in hybrid mode. No significant differences were found in the socioemotional challenges or in the balance of the metacognitive experience. CONCLUSION: The group that worked in hybrid learning valued group purposes over personal purposes and used the social regulation mechanism over individual regulation in conflict resolution. On the other hand, the group that worked virtually valued group and personal purposes equally and used the mechanism of individual regulation and social regulation to solve difficulties. Differences between students who worked in virtual and hybrid environments may be due to greater social interaction and group dynamics in hybrid environments, as well as differences in culture and access to resources and technology.

Operative Experience of Esophageal Surgery among General Surgery Residents in the United States: An Analysis of ACGME Operative Case Logs.

INTRODUCTION: Esophageal surgery is an essential component of general surgery training and encompasses several types of cases that are logged by general surgery residents. There is a scarcity of data on the quality and volume of esophageal surgery experience during surgical residency in the United States. We analyzed trends for 9 different esophageal procedure categories logged by residents in the United States, with the aim to identify areas for improvement in training. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from programs accredited by the ACGME over a fourteen-year period from 2009 to 2023. Data on mean esophageal cases reported by graduates, including mean in each procedure subcategory were retrieved. Cases were categorized as either surgeon chief or surgeon junior for each procedure category. Mann-Kendall trend test was used to obtain tau statistics and p-value for trends in mean operative surgical volume for the total number of cases in each operative category over the study period. Trends in surgeon chief and surgeon junior cases were also investigated for each operative category. RESULTS: The mean number of all esophageal procedures performed per resident during their training increased significantly from 10.5 in 2009 to 16 in 2022 (τ = 0.833, p < 0.001). This trend observed among all esophageal procedures during this 14-year study can be largely attributed to the steady increase in the number and proportion of laparoscopic esophageal antireflux procedures performed (τ = 0.950, p < 0.001). Additionally, esophagectomy procedures had a statistically significant, but modest, increase during the study period (τ = 0.505, p = 0.023), from a mean of 1 case during training in 2009 to a peak of 1.3 in 2020. Although the general trend of esophagus procedures increased during the study period, most categories (7 out of 9) either decreased or did not significantly change. Esophagogastrectomy volume decreased significantly by 30%, from 1 per resident during their training in 2009 to 0.7 in 2022 (τ = -0.510, p = 0.018), esophageal diverticulectomy procedures decreased by 50% from 0.2 to 0.1 (τ = -0.609, p = 0.009), and operations for esophageal stenosis decreased by 75% from 0.4 to 0.1 (τ = -0.734, p = 0.001). Mean number of esophageal bypasses (τ = -0.128, p = 0.584), repair of perforated esophageal disease (τ = -0.333, p = 0.156), and other major esophagus procedures (τ = 0.416, p = 0.063) did not significantly change. CONCLUSION: The operative volume of esophageal surgery that general surgery residents in the United States are exposed to has significantly risen over the past 14 years, largely driven by the increase in laparoscopic antireflux procedures. However, given the recent advances and the resultant heterogeneity in both esophageal surgery, the increase in resident operative volume is still inadequate to ensure the training of safe and adept esophageal surgeons, necessitating postresidency specialized training for trainees interested in esophageal surgery.

Trends in gastric surgery operative experience among general surgery residents in the United States: A nationwide retrospective analysis.

BACKGROUND: Gastric surgery is a crucial component of general surgery training. However, there is a paucity of high-quality data on operative volume and the diversity of surgical procedures that general surgery residents are exposed to. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from the American College of Graduate Medical Education-accredited program from 2009 to 2022. Data on the mean number of gastric procedures, including the mean in each subcategory, were retrieved. A Mann-Kendall trend test was used to investigate trends in operative volume. RESULTS: Between 2009 and 2022, the mean overall logged gastric procedures rose significantly (τ = 0.722, P < .001) from 36.2 in 2009 to 49.2 in 2022 (35.9% increase). The most substantial growth was seen in laparoscopic gastric reduction for morbid obesity (mean 1.9 in 2017 to 19 in 2022; τ = 0.670, P = .009). A statistically significant increase was also seen in laparoscopic partial gastric resections, repair of gastric perforation, and "other major stomach procedures" (P < .05 for all comparisons). Open gastrostomy, open partial gastric resections, and open vagotomy all significantly decreased (P < .05 for all comparisons). There was no significant change in the volume of laparoscopic gastrectomy, total gastric resections, and non-laparoscopic gastric reductions for morbid obesity (P > .05 for all comparisons). CONCLUSION: There has been a substantial increase in the volume of gastric surgery during residency over the past 14 years, driven mainly by an increase in laparoscopic gastric reduction. However, there may still be a need for further gastric surgical training to ensure well-rounded general surgeons.

In silico identification of a biarylamine acting as agonist at human ß3 adrenoceptors and exerting BRL37344-like effects on mouse metabolism.

Human ß3-adrenoceptor (ß3AR) agonists were considered potential agents for the treatment of metabolic disorders. However, compounds tested as ß3AR ligands have shown marked differences in pharmacological profile in rodent and human species, although these compounds remain attractive as they were successfully repurposed for the therapy of urinary incontinence. In this work, some biarylamine compounds were designed and tested in silico as potential ß3AR agonists on 3-D models of mouse or human ß3ARs. Based on the theoretical results, we identified, synthesized and tested a biarylamine compound (polibegron). In CHO-K1 cells expressing the human ß3AR, polibegron and the ß3AR agonist BRL 37344 were partial agonists for stimulating cAMP accumulation (50 and 57% of the response to isoproterenol, respectively). The potency of polibegron was 1.71- and 4.5-fold higher than that of isoproterenol and BRL37344, respectively. These results indicate that polibegron acts as a potent, but partial, agonist at human ß3ARs. In C57BL/6N mice with obesity induced by a high-fat diet, similar effects of the equimolar intraperitoneal administration of polibegron and BRL37344 were observed on weight, visceral fat and plasma levels of glucose, cholesterol and triglycerides. Similarities and differences between species related to ligand-receptor interactions can be useful for drug designing.